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Development of a fed-batch cultivation process for vaccine production against Neisseria meningitidis

Thursday 17 January 2013

Bas van de Waterbeemd, MSc (RIVM) and Mathieu Streefland, PhD (WUR)

The National Institute for Public Health and the Environment (RIVM) plays an important role in the prevention and control of infectious diseases. The vaccinology department is well equiped to respond to emerging diseases through the development of vaccines. The complete vaccine chain is present, from concept research to large-scale process development for clinical studies. We are developing a vaccine against Neisseria meningitidis, which accounts for approx. 80% of all bacterial meningitis cases in the Netherlands (100-400 cases per year).

Our vaccine concept is based on outer membrane vesicles (OMV), which are non-pathogenic, immunological lookalikes of the original bacterium. We have developed a robust and efficient pilot scale production process (40 L cultivation volume), but want to further improve the overall yield with a fed-batch cultivation. You will join the process development group and will learn to work with pathogenic bacteria in a ML-2 biosafety facility. The goal of your MSc thesis is to design and implement a fed-batch strategy. You will initially work with a 3L bioreactor system. If the strategy is successful, it will be tested at pilot scale.

We are looking for a motivated self-reliant student who can join us for at least six months, since the training in the ML-2 facility will require some time. Affinity or experience with process development, microbiology and immunology is recommended. You will receive a compensation of 550 gross per month. DTP vaccination (diphtheria, tetanus, poliomyelitis) is obligated.

Bas van de Waterbeemd
Scientist R&D Process Development
phone: 030 274 2278
email: bas.van.de.waterbeemd@rivm.nl

Relevant literature
Van de Waterbeemd B, Streefland M, et al. (2012) Identification and optimization of critical process parameters for the production of NOMV vaccine against Neisseria meningitidis. Vaccine 30: p3683-3690.

Van de Waterbeemd B, Streefland M, et al. (2010) Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process. Vaccine 28: p4810-6.

Van de Waterbeemd B, Streefland, M, et al. (2009) Gene-expression-based quality scores indicate optimal harvest point in Bordetella pertussis cultivation for vaccine production. Biotechnol Bioeng 103: 900-908.

Baart GJ, de Jong, G, et al. (2007) Scale-up for bulk production of vaccine against meningococcal disease. Vaccine 25: p6399-408.